Preparation of substituted acylanilides



Patented Aug. 24, 1948 PATENT OFFICE PREPARAifioNoF sUBsTiTiJTE-n ACYLANIL-IDES- Richard C. Clapp and Joliti iirai'iciio, staaiforgi,

Conn assignors to Amer:

i1 Cyaiiaiiiid pany, New York, N. Ya, a cdi'iiiir'atiiiiiof Maine The pres'ntinvention relates to cdiiipolirids I polycarboiiyli'c a'id anhydride, cal'boiidi stllphide,

and a Friedel Crafts" catalyst at atem'perature below about 50 G. The reaction may beillustrated by the following equation:

in which R is an alkyl radical and Z is an arylene radical or an alkylene radical such as (CH2)n wherein n is a small whole number of from 2 to 6.

The reaction mixture is maintained at a temperature of from about C. to about 50 C. for from about 36 hours to about 48 hours. While the initial reaction is complete in a matter of one-half to about three hours, we have found that in order to obtain the best yields of product the reaction mixture should stand from one and a half to two days.

We can use, as one of the intermediates, an hydride of polycarboxylic acids such as succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, phthalic acid, hexahydrophthalic acid, naphthalene-l,2-dicarboxylic acid, anthraquinone-l,2-dicarboxylic acid, anthracene-1,9- dicarboxylic acid, naphthalene-2,3-dicarboxylic acid, and the like.

For most purposes acetanilide is the preferred acylanilide although we can use other acylanilides such as propionalide, butyranilide, and other aliphatic acylanilides having up to about carbon atoms in the aliphatic chain.

Conventional Friedel-Crafts catalysts such as aluminum chloride, ferric chloride, stannous chloride, etc. may be used in the process.

The products can be purified by dissolving in alkaline solution, treating with norite and precipitating with acid. Further purification can be obtained by crystallizing the product from methanol, ethanol, propanol, acetic acid, and the like.

Most of the compounds of the present invention are useful as intermediates in the prepa- Application September Iii, i945 Serial No. 617,180

4 Claims. (Cl. 260-518) ration of compounds, having bacteriostatic properties, such as those described and claimed in our copending application Serial No. 546,205 filed July 22, 1944, now Patent #2,418,925 issued April 15, 1947.

Our invention will now be illustrated in greater detail by means of the following specific example showing the reaction of acetanilid-e with a representative pd'lycarboxyli c acid anhydride succifiie-annydrme). It will be understood, 6f course", that the example is given for pur sos sef illustration and is not to be considered as liiiiit ing our invention to the particular details described therein.

Ezamzble A suspension of 185 (1.39 mols) of aluminum chloride in 200 cc. of carbon disulfide (previously shaken with mercury) was prepared by grinding the granular product with the solvent in a mortar. The suspension was placed in a flask fitted with a Hershberg stirrer and a condenser and immersed in an ice bath. Fifty grams (0.37 mol) of acetanilide and 37 g. (0.37 mol) of succinic anhydride were ground together and the mixture was added rapidly to the aluminum chloride suspension with stirring. After the initial reaction had subsided, the cooling bath was removed and stirring was continued until the stiffness of the dark red mixture halted the stirrer (about two hours). After standing for two days at room temperature the mixture was decomposed with ice. The product was filtered off and washed well with water. The solid was dissolved in aqueous sodium bicarbonate and the solution was filtered. Acidification of the filtrate precipitated a yellow powder. The product obtained was beta-( l-acetylaminobenzoyl)- propionic acid (yield of theoretical) which after two crystallizations from alcohol had a melting point of 202-205 C. I

We claim:

1. A method of preparing compounds having the formula in which Z is a (CH-z) radical where n is a small whole number from 2 to 6 which comprises mix.

ing acetaniiide with a compound having the formula II o in which Z is as defined above, in the presence of 1o in which Z is a (CH2)n radical where n is a small whole number from 2 to 6 which comprises mixing acetanilide with a compound having the formula in which Z is as defined above, at a tempera are of from 0 to C. for from about 36 hours t 48 hours in the presence of a Friedel-Crafts catalyst and carbon disulfi-de.

4. A method of preparing gamma-(4-acetyL aminobenzoyD-butyric acid which comprises mixing acetanilide and glutaric anhydride at a temperature of from 0 to 50 C. for from about 36 hours to 48 hours in the presence of aluminum chloride and carbon disulfide.

RICHARD C. CLAPP. JOHN KRAPCHO.

, REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 1,654,290 Gubelmann Dec. 27, 1927 1,786,526 Groggins Dec. 30, 1930 2,071,496 Bruson et a1. Feb. 23, 1937 2,320,217 Bruson May 25,1943 2,394,230 Billman Feb. 5, 1946 OTHER REFERENCES Aioy et a1.: Bull. Soc. Chim. de France (4), vol. 9, page 762 (1911). Copy in Scientific Library. Kohier et a1.: Beilstein Handbuch der Org.

0 Chem., 4th ed., vol. 10, suppl., page 331 (1932).

Copy in Div. 6. 

